The research objectives of CSORDA are to gain insights into the mechanisms of action of endogenous opioids and opioid drugs at their cognate receptors with the goal of discerning fundamental processes contributing to behaviors such as analgesia, addiction, tolerance and withdrawal. The Center has four integrated components, which will investigate the activity of opioid ligands at the molecular, cellular and behavioral levels utilizing complementary methodologies and shared resources. The Components of CSORDA will specifically investigate: I) The regulation of trafficking and signaling of mu and delta receptors in vivo by high resolution imaging of mice expressing fluorescent receptors;II) The basis for mu ligand- directed signaling and receptor trafficking using primary dorsal root ganglia cells from wild-type as well as receptor and arrestin-deficient mice;III) The role of the endogenous opioid system in goal-directed and habitual behaviors both in drug free and opioid dependent conditions;IV) The functional regulation of transcripts in the striatonigral and striatopallidal projection neuron circuits and their relation to opioid drug reward. In addition to the research specified within the components, a Pilot Program will continue to create new avenues of investigation within the Center and enrich the ongoing programs. For facilitation of the component and pilot projects, an Administrative Core and the CSORDA Mouse Core (CMC), serve to integrate resources and coordinate the needs of the center. The overall mission of CSORDA is to enhance the understanding of the mammalian opioid system thereby providing strategies for improving the clinical use of opioids and treatments for addition.